CDC Yellow Book 2024Travel-Associated Infections & Diseases
INFECTIOUS AGENT: Yellow fever virus
Tropical South America
TRAVELER CATEGORIES AT GREATEST RISK FOR EXPOSURE & INFECTION
Avoid insect bites
Yellow fever is a vaccine-preventable disease
Yellow fever (YF) virus is a single-stranded RNA virus that belongs to the genus Flavivirus.
Vectorborne transmission of YF virus occurs via the bite of an infected mosquito, primarily Aedes or Haemagogus spp. Nonhuman primates and humans are the main reservoirs of the virus, and anthroponotic (human-to-vector-to-human) transmission occurs. YF virus has 3 transmission cycles: sylvatic (jungle), intermediate (savannah), and urban.
The sylvatic (jungle) cycle involves transmission of virus between nonhuman primates and mosquito species found in forest canopies. Virus is transmitted from monkeys to humans via mosquitoes when occupational or recreational activities encroach into the jungle. In Africa, an intermediate (savannah) cycle involves transmission of YF virus from tree hole–breeding Aedes spp. to humans in jungle border areas. YF virus can be transmitted from monkeys to humans or from human to human via these mosquitoes. The urban cycle involves transmission of virus between humans and peridomestic mosquitoes, primarily Ae. aegypti.
Humans infected with YF virus experience the highest levels of viremia shortly before onset of fever and for the first 3–5 days of illness, during which time they can transmit the virus to mosquitoes. Because of the high level of viremia, bloodborne transmission theoretically can occur via transfusion or needlesticks. One case of perinatal transmission of wild-type YF virus from a woman who developed symptoms of YF 3 days prior to delivery has been documented; the infant subsequently tested positive for YF viral RNA and died of fulminant YF on the 12th day of life.
YF occurs in sub-Saharan Africa and tropical South America, where it is endemic and intermittently epidemic (see Table 5-22 and Table 5-23 for lists of countries with risk of YF virus transmission). Most YF disease in humans is due to sylvatic or intermediate transmission cycles. Urban YF occurs periodically in Africa and sporadically in the Americas. In areas of Africa with persistent circulation of YF virus, natural immunity accumulates with age; consequently, infants and children are at greatest risk for disease. In South America, YF occurs most frequently in unimmunized young people exposed to mosquito vectors through their work in forested areas.
Table 5-22 Countries with risk for yellow fever (YF) virus transmission1
Democratic Republic of the Congo
1Current as of November 2022. Defined by the World Health Organization (WHO) as countries or areas where YF “has been reported currently or in the past and vectors and animal reservoirs currently exist.” See www.who.int/publications/m/item/countries-with-risk-of-yellow-fever-transmission-and-countries-requiring-yellow-fever-vaccination-(november-2022).
2These countries are not holoendemic (only a portion of the country has risk of YF virus + transmission). For details, see Map 5-10, Map 5-11, and YF vaccine recommendations (Sec. 2, Ch. 5, Yellow Fever Vaccine & Malaria Prevention Information, by Country).
Table 5-23 Countries with low potential for exposure to yellow fever (YF) virus1
São Tomé and Príncipe
1The countries on this list have low potential for exposure to YF virus and are not included on the World Health Organization list of countries with risk for YF virus transmission (Table 5-22). Unless a country requires proof of YF vaccination from all arriving travelers (Table 5-25), or specifies otherwise, proof of YF vaccination should not be required for travelers arriving from the countries on this list.
2Classified as “low potential for exposure to YF virus” only in some areas; remaining areas are classified as having no risk of exposure to YF virus.
Risk for Travelers
A traveler’s risk for acquiring YF is determined by their immunization status as well as destination-specific (e.g., local rate of virus transmission) and travel-associated (e.g., exposure duration, occupational and recreational activities, season) factors. Reported cases of human disease are the principal but crude indicator of disease risk. Case reports from a destination might be absent because of a low level of transmission, a high level of immunity in the population (e.g., due to vaccination), or failure of local surveillance systems to detect cases. Because “epidemiologic silence” does not mean absence of risk, travelers should not go into endemic areas without taking protective measures.
YF virus transmission in rural West Africa is seasonal; a period of elevated risk occurs at the end of the rainy season and the beginning of the dry season, usually July–October. In East Africa, YF virus transmission is generally less predictable because long periods (years) often pass between virus activity in this region; when YF virus transmission occurs in East Africa, seasonality is similar to that in West Africa.
The risk for infection by sylvatic vectors in South America is greatest during the rainy season (January–May, with a peak incidence during February and March). Ae. aegypti can transmit YF virus episodically, however—even during the dry season—in both rural and densely settled urban areas.
During 1970–2015, 11 cases of YF were reported in people from the United States and Europe who traveled to West Africa (6 cases) or South America (5 cases); 8 (73%) died. Only 1 traveler had a documented history of YF vaccination; that traveler survived. Starting in 2016, the number of travel-associated YF cases increased substantially, primarily because of outbreaks in Angola and Brazil. During 2016–mid-2021, >37 travel-associated cases were reported in unvaccinated travelers who were residents of nonendemic areas or countries, including ≥15 European travelers and 1 American traveler to Peru.
The risk of acquiring YF during travel is difficult to predict because of variations in ecologic determinants of virus transmission. For a 2-week stay, the estimated risk for illness and for death due to YF for an unvaccinated traveler visiting an endemic area are as follows: for West Africa, risk for illness is 50 per 100,000 and risk for death is 10 per 100,000; for South America, risk for illness is 5 per 100,000 and risk for death is 1 per 100,000. These estimates are based on the risk to resident populations, often during peak transmission season, and might not accurately reflect the risk to travelers who have a different immunity profile, follow mosquito bite precautions, have less outdoor exposure, or who travel during off-peak periods. A traveler’s risk for becoming infected is likely greater when outbreaks are occurring at their destination.
Most people infected with YF virus have minimal or no symptoms and are unlikely to seek medical attention. For those who develop symptomatic illness, the incubation period is typically 3–6 days. The initial illness is nonspecific: backache, chills, fever, headache, myalgia, nausea and vomiting, and prostration. Most improve after the initial presentation. After a brief remission of ≤48 hours, ≈12% of infected patients progress to a more serious form of the disease, characterized by hemorrhagic symptoms, jaundice, and eventually shock and multisystem organ failure. The case-fatality rate for severe cases is 30%–60%.
YF is a nationally notifiable disease. A preliminary diagnosis is based on clinical presentation and exposure details. Laboratory diagnosis is best performed by virus isolation or nucleic acid amplification tests (e.g., reverse transcription PCR [RT-PCR]) or by serologic assays. Perform virus isolation or nucleic acid amplification tests for YF virus or YF viral RNA early in the course of the illness. By the time more overt symptoms are recognized, the virus or viral RNA might no longer be detectable; thus, virus isolation and nucleic acid amplification testing should not be used to rule out a diagnosis of YF.
Serologic assays can be used to detect virus-specific IgM and IgG antibodies. Because of the possibility of cross-reactivity between antibodies against other flaviviruses, however, more specific antibody testing (e.g., a plaque reduction neutralization test) should be performed to confirm the infection. Contact your state or local health department or call the Centers for Disease Control and Prevention (CDC) Arboviral Diseases Branch at 970-221-6400 for assistance with diagnostic testing for YF virus infections.
No specific medications are available to treat YF virus infections; treatment is directed at symptomatic relief or life-saving interventions. Fluids, rest, and use of analgesics and antipyretics might relieve symptoms of aching and fever. Avoid prescribing medications than can increase the risk for bleeding (e.g., aspirin or other nonsteroidal anti-inflammatory drugs). During the first few days of illness, protect infected people from further mosquito exposure by keeping them indoors or under a mosquito net, so they do not contribute to the transmission cycle.
Personal Protective Measures
The best way to prevent mosquito-borne diseases, including YF, is to avoid mosquito bites (see Sec. 4, Ch. 6, Mosquitoes, Ticks & Other Arthropods).
YF is preventable by a relatively safe, effective vaccine. All YF vaccines currently manufactured are live attenuated viral vaccines. Only one YF vaccine (YF-VAX, Sanofi Pasteur) is licensed for use in the United States (Table 5-24). Periodically in the United States, shortages of YF-VAX have occurred due to production issues, including one that lasted from late 2015 until early 2021. To address this most recent shortage, Sanofi Pasteur collaborated with the CDC and the US Food and Drug Administration (FDA) to import and distribute Stamaril (a YF vaccine comparable to YF-VAX, manufactured at the company’s facility in France) under an expanded-access investigational new drug protocol.
The different YF vaccine products, including those manufactured outside the United States, have no substantial differences in reactogenicity or immunogenicity. Consider people who receive YF vaccines licensed in other countries but not approved by the FDA to be protected against YF. For the most current information on YF vaccine availability, check the CDC Travelers’ Health website.
Table 5-24 Vaccine to prevent yellow fever (YF)
TRADE NAME (MANUFACTURER)
YF-VAX (Sanofi Pasteur)
Not recommended for most people3
1Ages 6–8 months and ≥60 years are precautions, and age <6 months is a contraindication to receiving YF vaccine.
2YF-VAX is available in single-dose and multiple-dose (5-dose) vials.
3For further details regarding revaccination, see Prevention: Vaccine: Booster Doses, in this chapter.
Indications for Use
YF vaccine is recommended for people aged ≥9 months who are living in or traveling to areas with risk for YF virus transmission in Africa or South America. In addition, some countries require proof of YF vaccination for entry. For country-specific YF vaccination recommendations and requirements, see Sec. 2, Ch. 5, Yellow Fever Vaccine & Malaria Prevention Information, by Country.
Because of the risk for serious adverse events after YF vaccination, clinicians should only vaccinate people at risk for YF virus exposure or who require proof of vaccination to enter a country. To further minimize the risk for serious adverse events, carefully observe the contraindications and consider vaccination precautions before administering YF vaccine (Box 5-09). For additional information, refer to the YF vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP).
Box 5-09 Yellow fever vaccine contraindications & precautions
- Age <6 months
- Allergy to vaccine component1
- HIV infection (symptomatic) or CD4 T lymphocyte counts <200/mL (or <15% of total lymphocytes in children aged <6 years)2,3
- Primary immunodeficiencies
- Immunosuppressive and immunomodulatory therapies
- Malignant neoplasms
- Thymus disorder associated with abnormal immune cell function
- Age 6–8 months
- Age ≥60 years
- HIV infection (asymptomatic) and CD4 T lymphocyte counts 200–499/mL (or 15%–24% of total lymphocytes in children aged <6 years)2,3
1If considering vaccination, desensitization can be performed under direct supervision of a physician experienced in the management of anaphylaxis.
2Symptoms of HIV are classified in Centers for Disease Control and Prevention. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992;41(RR-17). Available from: www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm (see Table 1 Adults and Adolescents); and Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection 2010. pp. 20–2. Available from: www.hopkinsmedicine.org/som/faculty/appointments/_documents/_ppc_documents/portfolios/Hutton/Hutton-Portfolio-Samples/guidelines-for-the-use-of-antiretroviral-agents-in-pediatric-hiv-infection.pdf [PDF].
3In 2010, the Advisory Committee on Immunization Practices (ACIP) used this clinical classification of levels of immunosuppression among HIV-infected people to inform yellow fever vaccine recommendations (see Staples et al., Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices). A revised surveillance case definition for HIV infection was published in 2014. To date, ACIP has not updated YF vaccine recommendations for people infected with HIV.
For all eligible people, subcutaneously administer a single 0.5 mL injection of reconstituted vaccine, which is the standard dose.
Coadministration With Other Vaccines
No evidence exists that inactivated vaccines interfere with the immune response to YF vaccine. Therefore, inactivated vaccines can be administered either simultaneously or at any time before or after YF vaccination.
Live Attenuated Viral Vaccines
ACIP recommends that YF vaccine be given at the same time as other live viral vaccines. If simultaneous administration is not possible, wait 30 days between vaccinations, because the immune response to a live viral vaccine could be impaired if it is administered within 30 days of another live viral vaccine. One study demonstrated that coadministration of YF vaccine and measles-mumps-rubella (MMR) vaccine decreased the seroconversion ratios to all antigens, except measles. Two more recent studies also showed a less robust antibody concentration in people who seroconverted after vaccine coadministration. These studies suggest that whenever possible, it is best to give YF and MMR vaccines 30 days apart. Of greater importance, however, is ensuring that travelers are vaccinated appropriately before travel; coadministration of YF and MMR vaccines is therefore acceptable.
No data are available on the immune response to nasally administered live attenuated influenza vaccine given simultaneously with YF vaccine.
Live Bacterial Vaccines
Data suggest that oral Ty21a typhoid vaccine (Vivotif), a live bacterial vaccine, can be administered simultaneously or at any interval before or after YF vaccine. No data are available on the immune response to live attenuated oral cholera vaccine (Vaxchora) administered simultaneously with YF vaccine.
In recent years, several countries have extended vaccine supplies during large YF outbreaks by administering partial vaccine doses, usually 0.1 mL, a practice known as fractional dosing. Limited study data have demonstrated immunogenicity of fractional dosing is comparable to that of full-dose YF vaccination at 1 month and ≤1 year after subcutaneous administration; knowledge gaps regarding fractional dosing remain, however.
In the United States, FDA has not approved fractional dosing of YF vaccine. Furthermore, WHO notes that fractional dosing does not meet YF vaccination requirements under the International Health Regulations (IHR); proof of vaccination for international travel cannot be issued to a person who has received only a fractional dose.
In 2014, the WHO Strategic Advisory Group of Experts on Immunization concluded that a single primary dose of YF vaccine provides sustained immunity and lifelong protection against YF disease and that revaccination (a booster dose) is not needed. In 2016, the IHR were officially amended to specify that a completed International Certificate of Vaccination or Prophylaxis (ICVP or “yellow card”) is valid for the lifetime of the vaccinee, and countries cannot require proof of revaccination against YF as a condition of entry, even if the last vaccination was >10 years prior.
ACIP also has stated that a single dose of YF vaccine provides long-lasting protection and is adequate for most travelers. ACIP guidelines do differ slightly from those of WHO, however, by specifying that additional doses of YF vaccine are recommended for the following groups of travelers: people who were pregnant when they received their initial dose of vaccine (administer 1 additional dose before they are next at risk for YF); people who received a hematopoietic stem cell transplant after receiving a dose of YF vaccine (revaccinate before they are next at risk for YF as long as they are sufficiently immunocompetent); people infected with HIV when they received their last dose of YF vaccine (administer a dose every 10 years if they continue to be at risk for YF).
Consider administering a booster dose to travelers who received their last dose of YF vaccine ≥10 years previously if they will be going to higher-risk settings based on activities, duration of travel, location, and season. This consideration applies to travelers planning prolonged stays in endemic areas, those traveling to endemic areas (e.g., rural West Africa) during peak transmission season, or travelers visiting areas with ongoing outbreaks.
Although booster doses of YF vaccine are not recommended for most travelers, and despite the 2016 changes to the IHR, clinicians and travelers should nonetheless review the entry requirements for destination countries. For more information on country-specific recommendations and requirements, see Sec. 2, Ch. 5, Yellow Fever Vaccine & Malaria Prevention Information, by Country.
Common Adverse Reactions
Reactions to YF vaccine are generally mild; 10%–30% of vaccinees report mild systemic symptoms, including headache, low-grade fever, and myalgia, that begin within days after vaccination and last 5–10 days.
Serious Adverse Reactions
Immediate hypersensitivity reactions, characterized by bronchospasm, rash, or urticaria, are uncommon. Anaphylaxis after YF vaccine is reported to occur at a rate of 1.3 cases per 100,000 doses administered.
Yellow Fever Vaccine–Associated Neurologic Disease
Yellow fever vaccine–associated neurologic disease (YEL-AND) represents a collection of clinical syndromes, including acute disseminated encephalomyelitis, Guillain-Barré syndrome, meningoencephalitis, and, rarely, cranial nerve palsies. Historically, YEL-AND was diagnosed primarily among infants as encephalitis, although more recent case reports have described various neurological syndromes among people of most age groups. YEL-AND is rarely fatal.
Almost all cases of YEL-AND reported globally occur in first-time vaccine recipients. The onset of illness for documented cases in the United States is 2–56 days after vaccination. The incidence of YEL-AND in the United States is 0.8 per 100,000 doses administered, but is greater (2.2 per 100,000 doses) in people aged ≥60 years.
Yellow Fever Vaccine–Associated Viscerotropic Disease
Yellow fever vaccine–associated viscerotropic disease (YEL-AVD) is a severe illness similar to wild-type YF disease, in which vaccine virus proliferates in multiple organs, often leading to multiorgan dysfunction or failure and occasionally death. Since 2001, >100 confirmed and suspected cases of YEL-AVD have been reported throughout the world.
YEL-AVD has been reported to occur only after the first dose of YF vaccine; no laboratory-confirmed YEL-AVD has been reported after booster doses. For YEL-AVD cases reported in the United States, the median time from YF vaccination until symptom onset is 4 days (range 1–18 days). The case-fatality ratio is ≈48% and the incidence is 0.3 cases per 100,000 doses of vaccine administered. The incidence of YEL-AVD is greater for people aged ≥60 years (1.2 per 100,000 doses) and greater still for people aged ≥70 years.
Contraindications to receiving YF vaccine include age <6 months; various forms of altered immunity, including symptomatic HIV infection or HIV infection with severe immunosuppression; and hypersensitivity to vaccine components.
A person who has an absolute YF vaccine contraindication should not be vaccinated, because they have a condition that increases their risk for having a serious adverse event following vaccination. Encourage these people to consider alternative travel plans. If they cannot avoid travel to a YF-endemic area, provide them with a medical waiver (see below for details), emphasize the importance of strict adherence to protective measures against mosquito bites, and discuss risks associated with being unvaccinated.
Age Younger than 6 Months
YF vaccine is contraindicated in infants aged <6 months because the rate of YEL-AND is high, 50–400 cases per 100,000 infants vaccinated. The mechanism of increased neurovirulence in infants is unknown, but could be due to the immaturity of the blood–brain barrier, an increased or more prolonged viremia, or immune system immaturity. Travel to YF-endemic countries for children aged <6 months should be postponed or avoided.
Altered Immune Status
YF vaccine is contraindicated in people with AIDS or other clinical manifestations of HIV infection, including those with CD4 T lymphocyte counts <200/mL, or <15% of total lymphocytes for children <6 years old. This contraindication is based on the potential increased risk for encephalitis in this population. See the section on Precautions (later in this chapter) for guidance regarding HIV-infected people who do not meet the above criteria.
YF vaccine is contraindicated in people with a thymus disorder associated with abnormal immune cell function (e.g., myasthenia gravis, thymoma). There is no evidence of immune dysfunction or increased risk for YF vaccine–associated serious adverse events in people who have undergone incidental thymectomy or who have had indirect radiation therapy in the distant past; these people can be vaccinated.
YF vaccine is contraindicated in people who are immunodeficient or immunosuppressed, whether due to an underlying (primary) disorder or medical treatment. Organ transplant recipients and patients with malignant neoplasms are among those for whom YF vaccine is contraindicated (see Sec. 3, Ch. 1, Immunocompromised Travelers).
Immunosuppressive & Immunomodulatory Therapies
YF vaccine is contraindicated in people whose immunologic response is either suppressed or modulated by current or recent radiation therapy or drugs. Drugs with known immunosuppressive or immunomodulatory properties (Table 3-04) include, but are not limited to, alkylating agents, antimetabolites, high-dose systemic corticosteroids, interleukin blocking agents (e.g., anakinra, tocilizumab), monoclonal antibodies targeting immune cells (e.g., alemtuzumab, rituximab), or tumor necrosis factor-α inhibitors (e.g., etanercept).
People receiving therapies such as those listed above are presumed to be at increased risk for YF vaccine–associated serious adverse events; administration of live attenuated vaccines is contraindicated in the package insert for most of these drugs (see Sec. 3, Ch. 1, Immunocompromised Travelers). Even among people who have discontinued immunosuppressive or immunomodulatory therapies, defer administration of live viral vaccines until their immune function has improved. Family members of people with altered immune status who themselves have no contraindications can receive YF vaccine.
YF vaccine is contraindicated in people with a history of acute hypersensitivity reaction to a previous dose of the vaccine or to any of the vaccine components, including chicken proteins, eggs, egg products, or gelatin. If vaccination of a person with a questionable history of hypersensitivity to a vaccine component is considered essential, skin testing and, if indicated, desensitization should be performed by an experienced clinician according to instructions provided in the manufacturer’s vaccine prescribing information [PDF].
A person with a precaution (relative contraindication) to YF vaccine has a condition that might increase their risk for having a serious adverse event following vaccination, or that could interfere with the ability of the vaccine to produce immunity. YF vaccination precautions include age 6–8 months, age ≥60 years, asymptomatic HIV infection with moderate immunosuppression, pregnancy, and breastfeeding.
Discussing the benefits and risks of YF vaccination with all patients—but particularly those with underlying precautions—is an essential part of the pretravel consultation. If travel to a YF risk area is unavoidable for a person with a vaccine precaution, the discussion about vaccination should balance the risk for YF virus exposure against the risk for having a serious post-vaccination adverse event.
Solicit information from the traveler about their risk tolerance level, and include this in the shared decision making about whether to administer YF vaccine. If the decision is made not to vaccinate the traveler, provide a medical waiver, emphasize the critical importance of adhering to insect bite precautions, and discuss risks associated with being unvaccinated. When no risk for YF exists in the itinerary, but international travel requirements are in effect in the traveler’s destination(s), the vaccine risk outweighs the disease; avoiding vaccination and issuing a medical waiver to fulfill health regulations is reasonable, but this decision should be made in deliberation with the patient.
Age 6–8 Months
Two cases of YEL-AND have been reported in infants aged 6–8 months. By 9 months of age, risk for YEL-AND is believed to be substantially lower. ACIP recommends that, whenever possible, travel to YF-endemic countries for children aged 6–8 months should be postponed or avoided.
Age ≥60 Years
The rate of reported serious adverse events after YF vaccination in people aged ≥60 years is 7.7 per 100,000 doses distributed, compared with 3.8 per 100,000 for all YF vaccine recipients. The risks for YEL-AND and YEL-AVD are increased in this age group. Because YEL-AVD has been reported exclusively, and YEL-AND almost exclusively, in primary vaccine recipients, carefully consider the risks and benefits of vaccinating older travelers against YF vaccine for the first time.
Combined studies of >500 asymptomatic HIV-infected people classified as having moderate immune suppression, defined as CD4 T lymphocyte counts of 200–499/mL for people ≥6 years old (or 15%–24% of total lymphocytes for children aged <6 years) identified no serious adverse events after receipt of YF vaccine. HIV infection has, however, been associated with a reduced immunologic response to YF vaccine, and this diminished immune response has been correlated with HIV RNA levels and CD4 T cell counts.
If an asymptomatic HIV-infected person has no evidence of immune suppression based on CD4 counts (CD4 T lymphocyte counts ≥500/mL for people ≥6 years old or ≥25% of total lymphocytes for children aged <6 years), YF vaccine can be administered. Because YF vaccination might be less effective in eliciting an immune response in asymptomatic HIV-infected people, consider measuring their neutralizing antibody response to vaccination before travel. Contact your state health department or the CDC Arboviral Diseases Branch (970-221-6400) to discuss serologic testing.
Safety of YF vaccination during pregnancy has not been studied in any large prospective trials. In 2 observational studies of people vaccinated against YF during pregnancy, a slightly increased risk for minor congenital abnormalities (mainly pigmented nevi) was detected in one study, and a higher rate of spontaneous abortions was reported in the other. Neither finding was substantiated by subsequent studies.
If possible, pregnant people should avoid travel to YF risk areas. If travel is unavoidable and the risk for YF virus exposure is felt to outweigh the vaccination risk, recommending vaccination is appropriate. By contrast, if the vaccine risk is believed to outweigh the risk for YF virus exposure, suggest or offer a medical waiver to the traveler to fulfill health regulations.
The proportion of people vaccinated during pregnancy who develop a YF virus–specific IgG antibody response is variable depending on the study (39% or 98%) and might be correlated with the trimester when they received the vaccine. Because pregnancy can reduce immunologic responsiveness, consider serologic testing to document a protective immune response to the vaccine. Although no specific data are available, ACIP recommends that a person wait 4 weeks after receiving the YF vaccine before conceiving.
At least 3 YEL-AND cases have been reported in exclusively breastfed infants whose mothers were vaccinated with YF vaccine. All 3 infants were <1 month old at the time of exposure, and encephalitis was diagnosed in all 3 infants. Until specific research data are available, avoid vaccinating breastfeeding people against YF. When a person who is nursing cannot avoid or postpone travel to YF-endemic areas, however, recommend vaccination. Although no data are available to support the practice, some experts recommend that breastfeeding people should pump and discard their breast milk for ≥2 weeks after YF vaccination before resuming breastfeeding.
No data are available regarding possible increased occurrence of adverse events or decreased vaccine efficacy after YF vaccine administration in people with other chronic medical conditions that can affect immune response (e.g., diabetes mellitus, liver disease [including hepatitis C virus infection], or renal disease). Limited data suggest that autoimmune disease, either by itself or in conjunction with other risk factors, including immunosuppressive medication, could increase the risk for YEL-AVD. Therefore, use caution if considering vaccination of such patients. Factors to consider when assessing a patient’s general level of immune competence include clinical stability, comorbidities, complications, disease severity and duration, and which medications they are taking.
International Certificate Of Vaccination Or Prophylaxis
The IHR permit countries to require proof of YF vaccination documented on an ICVP (Figure 5-02) as a condition of entry for travelers arriving from certain countries, even if only in transit, to prevent YF virus importation and transmission in the destination country. Some countries require evidence of vaccination from all entering travelers, including those arriving directly from the United States (Table 5-25).
People with YF vaccine contraindications who must travel to destinations that require proof of vaccination should receive a medical waiver from a YF vaccine provider before their departure; see Medical Waivers (Exemptions) below. Travelers without proof of vaccination or a medical waiver arriving to destinations that require this documentation for entry could be denied entry or face mandatory quarantine (up to 6 days) or vaccination on site.
Figure 5-02 International Certificate of Vaccination or Prophylaxis (ICVP): instructions for completion1,2
1Clinics offering yellow fever vaccine can purchase ICVP (Form CDC 731; formerly PHS 731), from the US Government Publishing Office website or by phone (866-512-1800).
2Instructions for ICVP completion
(1) Print the traveler’s name exactly as it appears in their passport.
(2, 5, 7) Enter all dates in the format shown: day (in numerals), month (spelled in letters), year. In the example above, the patient’s date of birth is correctly entered as 22 March 1960.
(3) Space reserved for the patient’s signature.
(4) For yellow fever (YF) vaccination, print “Yellow Fever” in both spaces. If the ICVP is used to document proof of another required vaccination or prophylaxis (following an amendment to the International Health Regulations or by recommendation of the World Health Organization), write the disease or condition name in this space. Other vaccinations may be listed on the other side of the ICVP booklet.
(5) Enter the date of vaccine administration, as shown.
(6) The health care provider should enter their handwritten signature, as shown. A signature stamp is not acceptable. For yellow fever vaccine, the health care provider signing the ICVP may be the stamp owner, or another health care provider authorized by the stamp holder to administer or supervise the administration of the vaccine.
(7) The ICVP is valid beginning 10 days after the date of primary YF vaccination. Add that date to this box along with the suggested wording “life of person vaccinated,” as shown.
(8) Imprint the Uniform Stamp of the vaccinating center in this box.
Table 5-25 Countries that require proof of yellow fever (YF) vaccination from all arriving travelers1
1Current as of January 2023. Country requirements for YF vaccination are subject to change at any time; check with the destination country’s embassy or consulate before departure.
Anyone who received YF vaccination after December 15, 2007, must provide proof of vaccination on the new ICVP. If the person received the vaccine before December 15, 2007, their original International Certificate of Vaccination against Yellow Fever (ICV) card is still valid as proof of vaccination. Vaccinees should receive a completed ICVP, signed by the vaccine provider and validated with the stamp of the center where the vaccine was given. Failure to secure validations can cause a traveler to be denied entry, quarantined, or possibly revaccinated at the point of entry to a country.
A properly completed ICVP is valid beginning 10 days after the date of primary vaccination. As of July 2016, the YF vaccine booster requirement was eliminated in the IHR, and a completed ICVP is considered valid for the lifetime of the vaccinee. Clinics offering YF vaccine can purchase ICVPs (Form CDC 731; formerly PHS 731) from the US Government Publishing Office website or by phone (866-512-1800).
Designated Yellow Fever Vaccination Centers & Providers
The ICVP must bear the original signature of a YF vaccine provider, who can be a physician or other authorized licensed health care professional who supervises the administration of the vaccine. A signature stamp is not acceptable. YF vaccination must be given at a designated center that possesses an official “uniform stamp,” which must be used to validate the ICVP. In the United States, state and territorial health departments are responsible for designating nonfederal YF vaccination centers and issuing uniform stamps to YF vaccine providers. Information about the location and hours of YF vaccination centers is available from the CDC Travelers’ Health website.
Medical Waivers (Exemptions)
A YF vaccine provider issuing a medical waiver for YF vaccine should complete and sign the Medical Contraindications to Vaccination section of the ICVP (Figure 5-03). Reasons other than medical contraindications are not acceptable for exemption from vaccination. The YF vaccine provider should also provide the traveler with a signed and dated exemption letter on letterhead stationery, clearly stating the contraindications to vaccination and bearing the imprint of the uniform stamp used by the YF vaccination center to validate the ICVP. Risks associated with not being vaccinated should be discussed, and the importance of strict adherence to mosquito bite prevention measures emphasized.
Medical waivers might not be accepted by the destination country. To improve the likelihood that a border official will grant a waiver holder entry to their intended destination, recommend that travelers contact the local embassy or consulate of the country or countries well in advance of travel to obtain specific and authoritative advice regarding waiver documentation requirements. All information provided should be kept with the completed Medical Contraindications to Vaccination and waiver letter.
Figure 5-03 International Certificate of Vaccination or Prophylaxis (ICVP): Medical Contraindication to Vaccination section
Vaccine Requirements Versus Recommendations
Country entry requirements for proof of YF vaccination under the IHR differ from CDC’s recommendations. Countries are permitted to establish YF vaccine entry requirements to prevent the YF virus importation and transmission within their borders. Unless issued a medical waiver by a YF vaccine provider, travelers must comply with these requirements to enter the country.
Certain countries require vaccination from travelers arriving from all countries (Table 5-25); others require vaccination only for travelers above a certain age coming from countries with risk for YF virus transmission (see Sec. 2, Ch. 5, Yellow Fever Vaccine & Malaria Prevention Information, by Country). The WHO defines areas with risk for YF virus transmission as places where YF virus activity has been reported currently or in the past, and where vectors and animal reservoirs exist. Countries that contain areas with only low potential for YF virus exposure (Table 5-23) are not included on the official WHO list of countries with risk for YF virus transmission (Table 5-22). Unless a country requires proof of YF vaccination from all arriving travelers, proof of YF vaccination should not be required of travelers coming from countries identified as having low potential for YF virus exposure. Because country entry requirements are subject to change at any time, CDC encourages travelers and their health care providers to check with the relevant embassy or consulate before departure.
To make its recommendations for preventing travel-associated YF virus infections, CDC uses a destination-specific risk classification for YF virus transmission: endemic, transitional, low potential for exposure, and no risk. CDC recommends YF vaccination for travel to endemic or transitional areas (Map 5-10 and Map 5-11). Recommendations are subject to revision at any time because of changes in YF virus circulation; before departure, check the CDC Travelers’ Health website destination pages for current vaccine information and relevant Travel Health Notices.
CDC website: www.cdc.gov/yellowfever
Map 5-10 Yellow fever vaccine recommendations for Africa1,2
1Current as of November 2022. This map is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.
2Yellow fever (YF) vaccination is generally not recommended for travel to areas where the potential for YF virus exposure is low. Vaccination might be considered, however, for a small subset of travelers going to these areas who are at increased risk for exposure to YF virus due to prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites. Factors to consider when deciding whether to vaccinate a traveler include destination-specific and travel-associated risks for YF virus infection; individual, underlying risk factors for having a serious YF vaccine-associated adverse event; and country entry requirements.
Map 5-11 Yellow fever vaccine recommendations for the Americas1,2,3
1Current as of November 2022. This map is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.
2In 2017, the Centers for Disease Control and Prevention (CDC) expanded its yellow fever vaccine recommendations for travelers going to Brazil because of a large outbreak in multiple states in that country. For more information and updated recommendations, refer to the CDC Travelers’ Health website.
3Yellow fever (YF) vaccination is generally not recommended for travel to areas where the potential for YF virus exposure is low. Vaccination might be considered, however, for a small subset of travelers going to these areas who are at increased risk for exposure to YF virus due to prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites. Factors to consider when deciding whether to vaccinate a traveler include destination-specific and travel-associated risks for YF virus infection; individual, underlying risk factors for having a serious YF vaccine-associated adverse event; and country entry requirements.
The following authors contributed to the previous version of this chapter: Mark D. Gershman, J. Erin Staples
Gershman MD, Staples JE, Bentsi-Enchill AD, Breugelmans JG, Brito GS, Camacho LA, et al. Viscerotropic disease: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2012;30(33):5038–58.
Jentes ES, Poumerol G, Gershman MD, Hill DR, Lemarchand J, Lewis RF, et al. The revised global yellow fever risk map and recommendations for vaccination, 2010: consensus of the Informal WHO Working Group on Geographic Risk for Yellow Fever. Lancet Infect Dis. 2011;11(8):622–32.
Lindsey NP, Rabe IB, Miller ER, Fischer M, Staples JE. Adverse event reports following yellow fever vaccination, 2007–13. J Travel Med. 2016;23(5):taw045.
Monath TP, Cetron MS. Prevention of yellow fever in persons traveling to the tropics. Clin Infect Dis. 2002;34(10):1369–78.
Staples JE, Barrett ADT, Wilder-Smith A, Hombach J. Review of data and knowledge gaps regarding yellow fever vaccine-induced immunity and duration of protection. NPJ Vaccines. 2020;5(1):54.
Staples JE, Bocchini JA Jr, Rubin L, Fischer M. Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 20159;64(23):647–50.
Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59(RR-7):1–27.
Staples JE, Monath TP, Gershman MD, Barrett ADT. Yellow fever vaccine. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines, 7th edition. Philadelphia: Elsevier; 2018. pp. 1181–265.
World Health Organization. International health regulations, 2005. Geneva: The Organization; 2016. Available from: www.who.int/ihr/publications/9789241580496/en.
World Health Organization. Vaccines and vaccination against yellow fever. WHO position paper—June 2013. Wkly Epidemiol Rec. 2013;88(27):269–83.